Zika virus (ZIKV) is an arbovirus (vector-borne virus) of the genus Flaviviridae. Until recently, infections with ZIKV were thought to be mild and self-limiting. Since 2015 however, ZIKV infections have been associated with an increase in microcephaly and other birth defects in newborns following infection of the mother during pregnancy. More recently, it has been associated with Guillain-Barr Syndrome (GBS) in adults of both sexes. Increasing evidence points to ZIKV as the agent responsible for a variety of birth defects in newborns of mothers who become infected during pregnancy. However, the strength of the causal relationship of ZIKV infections in pregnancies with adverse outcomes of pregnancy has yet to be determined, and is the focus of an ongoing large, multicenter, international observational NIH study of the epidemiology, natural history, and pathogenesis of Zika in infants and pregnancy initiated in 2016. Another virus, the Human Immunodeficiency Virus (HIV), is the cause of Acquired Immunodeficiency Syndrome (AIDS), and likewise causes perinatal or congenital infection. Despite substantial progress in reducing maternal to child transmission (MTCT) of HIV, there still were more than 830,000 HIV infected pregnant women identified worldwide in 2015 by screening provided through the President?s Emergency Program for AIDS Relief (PEPFAR), and approximately 8,500 HIV-infected pregnant women give birth each year in the United States. The product of the intersection of these two epidemics is unknown at present. In contrast to HIV, the correlates of MTCT of ZIKV and the fetal disease caused by ZIKV infection are currently unknown. However, it seems likely that in HIV-infected pregnant women, HIV-related immune system dysfunction could be enhanced by acute viral infection, even in the presence of antiretroviral chemotherapy, and thereby increase the risk of MTCT both for HIV and ZIKV, and the adverse effects of fetal or neonatal infection. While remarkable progress in antiretroviral treatment for HIV-infected pregnant women now permits suppression of HIV levels, restoration of immune system function, and reduction of MTCT, the occurrence of ZIKV infection among HIV-infected pregnant women raises serious concerns for antiretroviral treatment?s effectiveness to suppress HIV and reduce risk of MTCT. Given that both HIV and ZIKV are neurotropic viruses, maintaining viral suppression for an HIV-infected pregnant woman may be critical for the health of her infant. An urgent need therefore exists to investigate the effects in pregnant women of HIV and ZIKV co-infection on mothers and infants alike, to delineate adverse effects and to develop recommendations for care that minimize adverse effects while allowing continuation of preventive therapy.